Favorable effects of omega-3 polyunsaturated fatty acids in attentional control and conversion rate to psychosis in 22q11.2 deletion syndrome

Armando, Marco; Ciampoli, Mariasole; Padula, Maria Carmela; Amminger, G. Paul; Crescenzo, Franco De; Maeder, Johanna; Schneider, Maude; Schaer, Marie; Managò, Francesca; Eliez, Stéphan; Papaleo, Francesco

doi:10.1016/j.neuropharm.2020.107995

Cited by 9 publications

(6 citation statements)

References 72 publications

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“…One per 100 patients with schizophrenia has 22q11.2 deletion [ 5 ]. The beneficial effects of omega-3 supplementation on attentional control and in transition to psychosis could support its early use in the 22q11DS population [ 66 ]. Pituitary dysmaturation is also present and could be associated with pleiotropic psychopathology and atypical neurodevelopment [ 67 ].…”

Section: Individual Levelmentioning

confidence: 99%

Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

Karbarz

2020

Genes

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Chromosomal 22q11.2 deletion syndrome (22q11.2DS) (ORPHA: 567) caused by microdeletion in chromosome 22 is the most common chromosomal microdeletion disorder in humans. Despite the same change on the genome level, like in the case of monozygotic twins, phenotypes are expressed differently in 22q11.2 deletion individuals. The rest of the genome, as well as epigenome and environmental factors, are not without influence on the variability of phenotypes. The penetrance seems to be more genotype specific than deleted locus specific. The transcript levels of deleted genes are not usually reduced by 50% as assumed due to haploinsufficiency. 22q11.2DS is often an undiagnosed condition, as each patient may have a different set out of 180 possible clinical manifestations. Diverse dysmorphic traits are present in patients from different ethnicities, which makes diagnosis even more difficult. 22q11.2 deletion syndrome serves as an example of a genetic syndrome that is not easy to manage at all stages: diagnosis, consulting and dealing with.

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Section: Individual Levelmentioning

confidence: 99%

Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

Karbarz

2020

Genes

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“…Polyunsaturated fatty acids (PUFAs) are fatty acids containing at least two carbon-carbon double bonds in their carboxylic chain, and classified into omega-3, omega-6 and omega-9 [15]. Their role in the prevention of cardiovascular diseases has been widely studied [15], while the interest for the use of PUFAs, especially considering eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), two omega-3 fatty acids, in the treatment of psychiatric diseases has been rising in recent years [16,17].…”

Section: Introductionmentioning

confidence: 99%

Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review

D’Alò

Crescenzo

Morgano

et al. 2020

Health Qual Life Outcomes

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Introduction: Some recent randomized controlled trials (RCTs) assessed the efficacy and safety of polyunsaturated fatty acids (PUFAs) for the treatment of autism spectrum disorder (ASD). To optimally inform the Italian guideline for the management of ASD in children and adolescents, we reviewed the impact on equity, acceptability and feasibility for developing a pilot recommendation for PUFAs. Methods: We performed a rapid systematic review of observational and experimental studies on PUFAs for children and adolescents with ASD, extracting data on resources required, equity, acceptability, and feasibility of PUFAs. We followed the framework provided by the grading of recommendations assessment, development and evaluation (GRADE) methodology, and we assessed risk of bias and methodological quality of included studies. Results were synthesized both narratively and quantitatively to address clinically relevant questions on equity, acceptability, and feasibility. Results: We found 14 papers related to equity. PUFAs did not seem to impact equity importantly. We did not find variation in effectiveness across subgroups and in a base case scenario, the cost of a 12 weeks cycle of therapy with 1.155 g/day of PUFAs was €65.51 euro. The acceptability of PUFAs was evaluated in 17 studies, 9 of which were RCTs. PUFAs were widely used among children and adolescents with ASD (18 to 51%), and 50% of parents considered nutritional supplementation as useful. Difficulty in swallowing capsules and bad taste were identified as possible causes of poor compliance, but treatment adherence, when measured in included RCTs, was judged to be good to excellent. Discontinuation due to any cause for PUFAs could not differ from placebo (low certainty of evidence). The feasibility of using PUFAs was assessed in 12 studies. PUFAs were probably sustainable, and no particular critical issue emerged from the feasibility assessment. However, the evidence appeared scarce and indirect.

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“…TCP and B12 can now be added to a growing list of drugs and compounds with proven ability to ameliorate the neuronal and/or behavioral deficits found in mouse models of 22q11.2DS ( Tamura et al, 2016 ; Nilsson et al, 2018 ; Fernandez et al, 2019 ; Mukherjee et al, 2019 ; Armando et al, 2020 ) and, in one case, in patients with 22q11.2DS ( Armando et al, 2020 ). To our knowledge, this study is the first to identify drugs that target TBX1 , the major candidate gene for 22q11.2DS, that have preventative potential in the mouse model.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Rescue of the Brain Cortex Phenotype of Tbx1 Mouse Mutants: Significance for 22q11.2 Deletion Syndrome

Favicchia

Flore

Cioffi

et al. 2021

Front. Mol. Neurosci.

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ObjectivesTbx1 mutant mice are a widely used model of 22q11.2 deletion syndrome (22q11.2DS) because they manifest a broad spectrum of physical and behavioral abnormalities that is similar to that found in 22q11.2DS patients. In Tbx1 mutants, brain abnormalities include changes in cortical cytoarchitecture, hypothesized to be caused by the precocious differentiation of cortical progenitors. The objectives of this research are to identify drugs that have efficacy against the brain phenotype, and through a phenotypic rescue approach, gain insights into the pathogenetic mechanisms underlying Tbx1 haploinsufficiency.Experimental ApproachDisease model: Tbx1 heterozygous and homozygous embryos. We tested the ability of two FDA-approved drugs, the LSD1 inhibitor Tranylcypromine and Vitamin B12, to rescue the Tbx1 mutant cortical phenotype. Both drugs have proven efficacy against the cardiovascular phenotype, albeit at a much reduced level compared to the rescue achieved in the brain.MethodsIn situ hybridization and immunostaining of histological brain sections using a subset of molecular markers that label specific cortical regions or cell types. Appropriate quantification and statistical analysis of gene and protein expression were applied to identify cortical abnormalities and to determine the level of phenotypic rescue achieved.ResultsCortical abnormalities observed in Tbx1 mutant embryos were fully rescued by both drugs. Intriguingly, rescue was obtained with both drugs in Tbx1 homozygous mutants, indicating that they function through mechanisms that do not depend upon Tbx1 function. This was particularly surprising for Vitamin B12, which was identified through its ability to increase Tbx1 gene expression.ConclusionTo our knowledge, this is only the second example of drugs to be identified that ameliorate phenotypes caused by the mutation of a single gene from the 22q11.2 homologous region of the mouse genome. This one drug-one gene approach might be important because there is evidence that the brain phenotype in 22q11.2DS patients is multigenic in origin, unlike the physical phenotypes, which are overwhelmingly attributable to Tbx1 haploinsufficiency. Therefore, effective treatments will likely involve the use of multiple drugs that are targeted to the function of specific genes within the deleted region.

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Favorable effects of omega-3 polyunsaturated fatty acids in attentional control and conversion rate to psychosis in 22q11.2 deletion syndrome

Cited by 9 publications

References 72 publications

Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

Consequences of 22q11.2 Microdeletion on the Genome, Individual and Population Levels

Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review

Pharmacological Rescue of the Brain Cortex Phenotype of Tbx1 Mouse Mutants: Significance for 22q11.2 Deletion Syndrome

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